The rapid advances in molecular biology and cell culture techniques have expanded our understanding of the mechanisms regulating cell growth and differentiation. At the same time, our ability to apply molecular biology techniques and reagents developed in vitro to the in vivo, cellular environment have lagged behind. Most studies have relied upon either vehicle-mediated transfer or facilitator-aided transport. These standard procedures work well for many cell lines, but provide little control over dose, require large numbers of cells and tend to perturb cell physiology. The advent of semi-automatic microinjection of cells in culture represents a technological bridge linking the most advanced techniques of molecular biology and cell culture model systems. In microinjection, the computer controlled movements of the glass micropipette penetrate the cell membrane to directly deliver to the cytoplasmic or nuclear compartment a wide variety of reagents by controlled volume displacement. Many of these reagents would not be able to normally enter the cell and reach their target molecules or the transfer method would require a large number of cells and in many cases, affect cell metabolism and phenotypic response. Thus, microinjection allows rapid and easy transfer of specific quantities of antibodies, proteins, RNA or DNA molecules. The automatic, computer controlled micromanipulation procedure permits the injection of up to 1-2000 cells per hour making possible reliable statistical evaluation of cell responses to injected reagents. This instrumentation will permit functional analysis of critical molecular processes that govern cell proliferation and differentiation. By directly manipulating levels of cellular macromolecules, it will be possible to unequivocally demonstrate causal relationships. We are proposing to set up at UCLA a Cell Microinjection System Core Facility that will serve the needs of an initial group of 9 cellular and molecular biology research groups. The enhancement of research through the application of this shared instrument is described in nine research projects.